Submissions for variant NM_001077365.2(POMT1):c.1598C>T (p.Ala533Val)

gnomAD frequency: 0.00024  dbSNP: rs199682341

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000712813	SCV000703116	uncertain significance	not provided	2016-10-29	criteria provided, single submitter	clinical testing
Invitae	RCV000695707	SCV000824222	uncertain significance	Autosomal recessive limb-girdle muscular dystrophy type 2K; Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1; Walker-Warburg congenital muscular dystrophy	2022-10-04	criteria provided, single submitter	clinical testing	This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 555 of the POMT1 protein (p.Ala555Val). This variant is present in population databases (rs199682341, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with POMT1-related conditions. ClinVar contains an entry for this variant (Variation ID: 498220). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt POMT1 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Athena Diagnostics	RCV000712813	SCV000843347	uncertain significance	not provided	2018-05-16	criteria provided, single submitter	clinical testing
GeneDx	RCV000712813	SCV001993786	uncertain significance	not provided	2019-05-14	criteria provided, single submitter	clinical testing	In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute	RCV002470918	SCV002767589	uncertain significance	Myopathy caused by variation in POMT1	2019-08-28	criteria provided, single submitter	clinical testing	A heterozygous missense variant was identified, NM_007171.3(POMT1):c.1664C>T in exon 17 of 20 of the POMT1 gene. This substitution is predicted to create a minor amino acid change from alanine to valine at position 555 of the protein NP_009102.3(POMT1):p.(Ala555Val). The alanine at this position has low conservation (100 vertebrates, UCSC), and is located within the PMT_4TMC functional domain. In silico software predicts this variant to be benign (Polyphen, SIFT, CADD, Mutation Taster). The variant is present in the gnomAD population database at a frequency of 0.01% (37 heterozygotes, 0 homozygotes). The variant has been previously reported as a variant of uncertain significance (VUS) in ClinVar. Based on information available at the time of curation, this variant has been classified as a VARIANT of UNCERTAIN SIGNIFICANCE (VUS) with LOW CLINICAL RELEVANCE.
Fulgent Genetics, Fulgent Genetics	RCV002491186	SCV002784439	uncertain significance	Autosomal recessive limb-girdle muscular dystrophy type 2K; Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1; Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1	2022-04-04	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000712813	SCV003811842	uncertain significance	not provided	2019-09-09	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000712813	SCV004156575	likely benign	not provided	2022-05-01	criteria provided, single submitter	clinical testing	POMT1: BP4